Tert-Butyl nitrite → HCID 89761998, compound

Participants

Reaction Steps

To a solution of 4-(4-amino-2-bromophenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.095 g, 0.162 mmol) in dry acetonitrile (1.617 mL) at 0° C. was added tert-butyl nitrite (0.027 mL, 0.226 mmol), followed by dropwise addition of azidotrimethylsilane (0.026 mL, 0.194 mmol). The resulting mixture was stirred for 20 minutes at RT. The reaction was concentrated under a vacuum, and purified via silica gel MPLC, eluting with a gradient of 0% to 100% ethyl acetate in heptanes to provide 4-(4-azido-2-bromophenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide as tan solid. The material was taken up in DCM (1.5 mL), and TFA (0.125 mL, 1.617 mmol) was added. The reaction was stirred at RT for 1.5 h, after which the reaction was concentrated under a vacuum. The material was purified by reverse-phase preparative HPLC using a Phenomenex Luna column, 5 micron, C18(2), 100 Å, 150×30 mm, 0.1% TFA in CH3CN/H2O, gradient 30% to 90% over 20 min to provide 4-(4-azido-2-bromophenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide 2,2,2-trifluoroacetate (0.0308 g, 0.051 mmol) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.55-3.63 (m, 1 H) 3.64-3.72 (m, 1 H) 4.27-4.34 (m, 1 H) 4.35-4.41 (m, 1 H) 6.10 (d, J=8.41 Hz, 1 H) 6.78 (d, J=4.69 Hz, 1H) 7.08-7.15 (m, 2 H) 7.22 (d, J=4.60 Hz, 1 H) 7.28 (dd, J=8.51, 2.54 Hz, 1 H) 7.53 (d, J=8.51 Hz, 1 H) 7.56 (d, J=2.54 Hz, 1 H) 12.55 (br. s., 1 H). m/z (ESI) 493.0 (M+H)+.

Provenance & Evidence